Event details

This meeting celebrates the 100th anniversary of the discovery that cells require adhesion to a solid surface to grow outside the animal organ. As new culturing techniques now allow organ growth in the laboratory, it is timely to discuss cell adhesion in relation to implantation, cancer, tooth decay, parasitic diseases, bacteria, virus attack, nanoparticle toxicity, theory, computer modelling, ethics and many related topics. The outcomes will impact across all scientific disciplines.

Biographies of the organisers and speakers are available below. Recorded audio of the presentations will be available on this page after the event and the papers will be published in a future issue of Philosophical Transactions B.

This meeting is immediately followed by a related satellite meeting at the Royal Society at Chicheley Hall, home of the Kavli Royal Society International Centre.

Attending this event

This event is intended for researchers in relevant fields and is free to attend. There are a limited number of places and registration is essential. An optional lunch is offered and should be booked during registration (all major credit cards accepted).

Organisers

Biography

Professor Kevin Kendall received his PhD from Cambridge and has worked for 20 years in industrial research at ICI, and also 20 years in Universities at Monash, Akron, Keele and now Birmingham. He started his research career studying friction and adhesion and became interested in the energy balance method for calculating adhesion forces. He has applied this method to many different areas including adhesive joints, composites, slurries, nanoparticles, cells and viruses. He has also been involved in the fossil energy crisis and applies fuel cells to avoid carbon emissions, especially operating a fleet of hydrogen fuel cell vehicles with a filling station on the Birmingham University campus as shown in the picture. He is now back in industry, CEO of Adelan Ltd, an SME developing several EU projects. He has written more than 300 publications and patents and was elected FRS in 1993.

Professor Costantino Creton, ESPCI CNRS, France

Professor Costantino Creton, ESPCI CNRS, France

Biography

Costantino Creton graduated in Materials Science from the EPFL (Switzerland) in 1985. He then obtained his PhD in Materials Science and Engineering at Cornell University (USA). After a post-doc at the IBM Almaden Research Center (USA), he joined the ESPCI ParisTech first as a post-doctoral associate in 1993 and, since 1994 as a C.N.R.S. permanent researcher. He was promoted CNRS research director (equivalent to Professor) in 2001and since 2009, he is coordinating the research activities of the Soft Polymer Networks research group of the laboratory. He holds also since 2011 the position of scientific chairman of the Performance Polymers technology area of the Dutch Polymer Institute. He has published more than 130 articles in peer-reviewed journals, nine book chapters, more than 100 conference proceedings and has given more than 70 invited and plenary lectures at international conferences.

Dr Florian Rehfeldt, Georg-August University Goettingen, Germany

Dr Florian Rehfeldt, Georg-August University Goettingen, Germany

Biography

Florian Rehfeldt, born in 1975 in Munich, Germany, studied Physics at the Technische Universität München (TUM) in Germany and received his PhD in Physics in 2005 for his work on “Novel Ultrathin Polymer Films as Biomimetic Interfaces” working with Prof. Dr. Motomu Tanaka and Prof. Dr. Erich Sackmann at the Institute for Biophysics E22. In 2006, he moved to University of Pennsylvania in Philadelphia to work with Prof. Dr. Dennis E. Discher on cell mechanics and the design of biomimetic hydrogels as in vitro culture systems with well-defined elasticity and was awarded a Feodor-Lynen-fellowship of the Alexander-von-Humboldt foundation. He returned to Germany end of 2008 and worked as a senior post-doctoral fellow in the 3rd Institute of Physics – Biophysics directed by Prof. Dr. Christoph F. Schmidt at the Georg-August-University in Göttingen. Since 2011 he is leading the Cell & Matrix Mechanics group in this institute and aims at elucidating the complex interplay of mechanics and biochemistry determining cell behavior.

Professor Gabriel Waksman FRS

Professor Gabriel Waksman FRS

Biography

Gabriel Waksman obtained his PhD in 1982 from the University of Paris. After a short spell in industry and a postdoctoral training at the Rockefeller University in New York, he joined the faculty of Washington University School of Medicine (St Louis, USA) in 1993. In 2000, he became the Alumni Endowed Professor of Biochemistry and Molecular Biophysics, and in 2002 was appointed the first Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics. In 2003, he moved to London (UK) to take up the Joint Chair of Structural and Molecular Biology at University College London and Birkbeck College London. The same year, he was awarded a Wolfson-Royal Society Merit Award and was appointed the Head of the Institute of Structural and Molecular Biology at UCL/Birkbeck. In 2006, he was appointed to the Courtauld Chair in Biochemistry at UCL, became Head of the Department of Biochemistry and Molecular Biology (now Research Department of Structural and Molecular Biology) at UCL and was appointed Head of the School of Crystallography (now Department of Biological Sciences) at Birkbeck. He was elected to EMBO in 2007, a Fellow of the Academy of Medical Sciences in 2008, a Fellow of the Royal Society in 2012, and a member of the German Academy of Sciences in 2013, He maintains an active research programme in the Structural and Molecular Biology of Bacterial Secretion Systems funded by a senior investigator award from the Wellcome Trust, an Advanced ERC grant, and a programme grant from MRC.

Dr Walter Federle, University of Cambridge, UK

Dr Walter Federle, University of Cambridge, UK

Biography

Dr Walter Federle is a Senior Lecturer for Integrative and Comparative Biology at the Department of Zoology, University of Cambridge, UK. Following his Diploma in Biology he obtained his PhD in 1998 from the University of Würzburg, Germany. He was a Postdoctoral Scholar at Harvard University, Cambridge, USA, and the University of California, Berkeley, USA, as well as at the University of Würzburg. Since joining the Department of Zoology at the University of Cambridge in 2005, his research has focused on the role of mechanical factors in insect-plant interactions, as well as on animal biomechanics and the biophysics of biological adhesion.

Session 1: van der Waals adhesion influencing organisms

Biography

Professor Kevin Kendall received his PhD from Cambridge and has worked for 20 years in industrial research at ICI, and also 20 years in Universities at Monash, Akron, Keele and now Birmingham. He started his research career studying friction and adhesion and became interested in the energy balance method for calculating adhesion forces. He has applied this method to many different areas including adhesive joints, composites, slurries, nanoparticles, cells and viruses. He has also been involved in the fossil energy crisis and applies fuel cells to avoid carbon emissions, especially operating a fleet of hydrogen fuel cell vehicles with a filling station on the Birmingham University campus as shown in the picture. He is now back in industry, CEO of Adelan Ltd, an SME developing several EU projects. He has written more than 300 publications and patents and was elected FRS in 1993.

Abstract

Adhesion molecules have been thought to control the adhesion of cells [1]. Unfortunately, the ‘lock and key’ model is unacceptable. While there is no doubt that a coating of adhesion molecules such as fibronectin on a surface affects cell adhesion, this is only one factor in the equation. Van der Waals force is the key cause of cell adhesion and is purely electromagnetic. Substrate elasticity and geometry are also important. Originally, the theoretical ideas were defined [2,3] in 1970-1971. By considering the contact of elastic bodies, it became evident that three parameters generally entered the equation for adhesive force F, as indicated below.

F = K [WEd3/(1-2)] 1/ (1)

where K was a constant, W the work of adhesion in Jm

-2, E the elastic modulus in Pa,  the Poisson’s ratio and d the dimension in metres. From this model, it is clear that the adhesion molecules have an effect on W, but elasticity E is equally influential and the geometry d is much more important. The most surprising thing about this new theory was that adhesion force was strongest when the surfaces were absolutely smooth and clean, with no projecting ‘lock and key’ and no adhesion molecules present. In other words the effect of adhesion molecules was to reduce the adhesion force, not to cause it.

Biography

Professor Autumn's research focus lies at the interface of biology (biomechanics), engineering (contact mechanics and materials science), and physics (intermolecular and interfacial forces. He is best known for discovering how geckos stick to walls and for inventing the adhesive nanostructure. Prof. Autumn received his Bachelor’s degree in Mathematics and Biology at the University of California at Santa Cruz in 1988, and his Ph.D. in Integrative Biology at UC Berkeley in 1995. He was an Office of Naval Research Postdoctoral Fellow until 1998, when he joined the faculty of Biology at Lewis & Clark in Portland, Oregon. Prof. Autumn has authored over 60 papers, and Thompson/ISI lists him as a highly cited author in the field of Materials Science and Engineering. He is the recipient of a National Science Foundation Special Creativity Award.

Abstract

Geckos climb at speeds of over 1 m/s using adhesive nanostructures on their toes. Gecko toes bear angled arrays of branched, setae formed from stiff, hydrophobic beta-keratin that act as a soft bed of angled springs. Previously, we discovered that setae form a self-cleaning, anisotropic, mechanically switchable adhesive that adheres by van der Waals forces. Subsequently, we showed that humidity softens

and increases viscoelastic losses in setal keratin, increasing van der Waals adhesion. We employed the humidity effect on setal materials properties to test dynamic friction models for multicontact interfaces. Contact forces were materials-dependent domain at low velocity (< 1 mm/s) and materials-independent at higher velocity. This supports the rate-state model of sliding friction, in which shear force is the result of competition between rate-enhancing and contact-area-enhancing mechanisms. Natural and synthetic gecko setae can be employed as a model system in the study of interfacial forces. Smart materials properties of gecko-inspired adhesive nanostructures may enable rigid, inert, recyclable materials to replace glues, screws, and other attachment devices in the future.

Biography

Dr Walter Federle is a Senior Lecturer for Integrative and Comparative Biology at the Department of Zoology, University of Cambridge, UK. Following his Diploma in Biology he obtained his PhD in 1998 from the University of Würzburg, Germany. He was a Postdoctoral Scholar at Harvard University, Cambridge, USA, and the University of California, Berkeley, USA, as well as at the University of Würzburg. Since joining the Department of Zoology at the University of Cambridge in 2005, his research has focused on the role of mechanical factors in insect-plant interactions, as well as on animal biomechanics and the biophysics of biological adhesion.

Abstract

Adhesive pads of climbing animals provide interesting models for synthetic adhesives as they work under the most challenging conditions, including rough, wet or dirty substrates and extremely rapid attachment and detachment during locomotion. Adhesion is controlled dynamically via the directionality and shear force dependence of climbing pads. Insect adhesive organs make contact when pulled towards the body, and their adhesion increases linearly with pulling force, but they detach when pushed. Nevertheless, climbing insects can use their feet for pushing; they have evolved specialised "heel" pads for this purpose.

Although high friction is essential for insect adhesion, insects inject small volumes of fluid into the pad contact zone. In insects with smooth pads, this fluid is a water-in-oil emulsion which helps to reduce slipping. The secretion does not generally increase adhesion, but it helps to maximise contact area on rough substrates and allows insects to maintain strong adhesion during sliding. However, some specialised plant surfaces are lubricated and cause insects to slip.

Biography

Erich Sackmann received his Diploma in Physics in 1961 and did his PhD in Physics in 1964 with Professor Theodor Förster (the discoverer of energy transfer, FRET) at University of Stuttgart. He worked for two years as a Member of Technical Staff at Bell Telephone Laboratories in Murray Hill and 5 years at the Max Planck Institute for Biophysical Chemistry in Göttingen. From 1974 -1980 he was professor of physics and head of the biophysics department at the University of Ulm and from 1980 to 2003 he held the same position at the Physics Department of the Technical University Munich. Presently he is Professor Emeritus at the Technical University Munich.

Research interest: From 1965 to 1970: Physics of liquid crystals and photophysics of organic solid state. Since 1970: Biological Physics with special emphasize on physics of biological membranes, cell adhesion and cell mechanics.

Adhesion domains form by clustering of CAMs (mediated by lateral phase separation) and are stabilized by coupling of CAM-clusters to the intracellular macromolecular network of the actin filaments and the aster-like assembly of microtubules.

Adhesion domains enable cells to form strong adhesion domains by commitment of some 10,000 receptors. Together with the actin-microtubule crosstalk this enables cells to polarize and move by ongoing formation and dismantling of adhesion domains with a minimum of material turnover. Cell polarization and locomotion can be understood in terms of a shell-string model of cells.

Biography

Erich Sackmann received his Diploma in Physics in 1961 and did his PhD in Physics in 1964 with Professor Theodor Förster (the discoverer of energy transfer, FRET) at University of Stuttgart. He worked for two years as a Member of Technical Staff at Bell Telephone Laboratories in Murray Hill and 5 years at the Max Planck Institute for Biophysical Chemistry in Göttingen. From 1974 -1980 he was professor of physics and head of the biophysics department at the University of Ulm and from 1980 to 2003 he held the same position at the Physics Department of the Technical University Munich. Presently he is Professor Emeritus at the Technical University Munich.

Research interest: From 1965 to 1970: Physics of liquid crystals and photophysics of organic solid state. Since 1970: Biological Physics with special emphasize on physics of biological membranes, cell adhesion and cell mechanics.

Biography

Florian Rehfeldt, born in 1975 in Munich, Germany, studied Physics at the Technische Universität München (TUM) in Germany and received his PhD in Physics in 2005 for his work on “Novel Ultrathin Polymer Films as Biomimetic Interfaces” working with Prof. Dr. Motomu Tanaka and Prof. Dr. Erich Sackmann at the Institute for Biophysics E22. In 2006, he moved to University of Pennsylvania in Philadelphia to work with Prof. Dr. Dennis E. Discher on cell mechanics and the design of biomimetic hydrogels as in vitro culture systems with well-defined elasticity and was awarded a Feodor-Lynen-fellowship of the Alexander-von-Humboldt foundation. He returned to Germany end of 2008 and worked as a senior post-doctoral fellow in the 3rd Institute of Physics – Biophysics directed by Prof. Dr. Christoph F. Schmidt at the Georg-August-University in Göttingen. Since 2011 he is leading the Cell & Matrix Mechanics group in this institute and aims at elucidating the complex interplay of mechanics and biochemistry determining cell behavior.

Abstract

The mechanical properties of microenvironments in our body are very diverse and are as important to cells as biochemical cues. An especially striking experiment of this mechano-sensitivity demonstrated that the Young’s modulus E of the substrate directs the lineage differentiation of human mesenchymal stem cells (hMSCs).

I will show how a novel biomimetic ECM model based on hyaluronic acid (HA) that exhibits a widely tuneable and well-defined elasticity E, enables 2D and 3D cell culture to mimic a variety of distinct in vivo microenvironments. Quantitative analysis of the structure of acto-myosin fibres of hMSCs on elastic substrates, reveals that stress fibre morphology is an early morphological marker of mechano-guided differentiation. Furthermore, the cytoskeleton also dictates the shape of the nucleus and lends support to a direct mechanical matrix-myosin-nucleus pathway.

Memberships and Fellowships: Member, American Academy of Arts and Sciences, National Academy of Sciences, National Academy of Engineering, American Philosophical Society; Fellow of the American Association for the Advancement of Science, Institute of Physics, American Physical Society, New York Academy of Sciences, World Technology Network, and American Chemical Society; Foreign Fellow of the Indian National Academy of Science; Honorary Member of the Materials Research Society of India; Honorary Fellow of the Chemical Research Society of India, Royal Netherlands Academy of Arts and Sciences, Royal Society of Chemistry (UK); Foreign Associate of the French Academy of Sciences; Honorary Professor, Academy of Scientific and Innovative Research (AcSIR), India.

Session 3: Parasites adhering to and entering cells

Biography

Gabriel Waksman obtained his PhD in 1982 from the University of Paris. After a short spell in industry and a postdoctoral training at the Rockefeller University in New York, he joined the faculty of Washington University School of Medicine (St Louis, USA) in 1993. In 2000, he became the Alumni Endowed Professor of Biochemistry and Molecular Biophysics, and in 2002 was appointed the first Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics. In 2003, he moved to London (UK) to take up the Joint Chair of Structural and Molecular Biology at University College London and Birkbeck College London. The same year, he was awarded a Wolfson-Royal Society Merit Award and was appointed the Head of the Institute of Structural and Molecular Biology at UCL/Birkbeck. In 2006, he was appointed to the Courtauld Chair in Biochemistry at UCL, became Head of the Department of Biochemistry and Molecular Biology (now Research Department of Structural and Molecular Biology) at UCL and was appointed Head of the School of Crystallography (now Department of Biological Sciences) at Birkbeck. He was elected to EMBO in 2007, a Fellow of the Academy of Medical Sciences in 2008, a Fellow of the Royal Society in 2012, and a member of the German Academy of Sciences in 2013, He maintains an active research programme in the Structural and Molecular Biology of Bacterial Secretion Systems funded by a senior investigator award from the Wellcome Trust, an Advanced ERC grant, and a programme grant from MRC.

Abstract

Gram-negative pathogens commonly exhibit adhesive pili on their surface that mediate specific attachment to the host. A major class of pili is assembled via the chaperone/usher (CU) pathway. Type 1 and P pili have served as model systems for the elucidation of the CU biosynthetic pathway. Pilus assembly requires a periplasmic chaperone (FimC and PapD for type 1 and P pili, respectively) and an outer-membrane assembly platform termed “usher” (FiimD and PapC for type 1 and P pili, respectively). CU pilus subunits are produced in the cytoplasm, translocated to the periplasm by the Sec translocation machinery, and then taken up by a chaperone to cross the periplasmic space to reach the outer-membrane. At the outer-membrane, chaperone-subunit complexes are recruited to an outer-membrane assembly platform, the usher, which orchestrates recruitment and polymerization of subunits. Previous work has elucidated the molecular basis of chaperone function. Recent progress has shed light into the mechanism of pilus subunit assembly at the usher, leading to the elucidation of the entire cycle of pilus subunit incorporation.

Biography

Stanislav Gorb is a group leader at the Zoological Institute of the University of Kiel, Germany. He received his PhD degree in zoology and entomology at the Schmalhausen Institute of Zoology of the Ukrainian Academy of Sciences in Kiev, Ukraine. Gorb was a postdoctoral researcher at the University of Vienna, Austria, a research assistant at University of Jena, a group leader at the Max Planck Institutes for Developmental Biology in Tübingen and for Metals Research in Stuttgart, Germany.

Gorb’s research focuses on morphology, structure, biomechanics, and evolution of surface-related functional systems in animals and plants, as well as the development of biologically inspired technological surfaces and systems. He received the Schlossmann Award (1995), Science Award of the Donors’ Association for the Promotion of Science in Germany (2005), International Forum Design Gold Award (2011); Materialica "Best of" Award (2011), Transfer-Price of Schleswig-Holstein (2011) and was the BioFuture Competition winner for his works on biological attachment devices (1998). Gorb has authored three books; more than 300 papers in peer-reviewed journals; and four patents. He is corresponding member of Academy of the Science and Literature Mainz (since 2010), Germany and member of the National Academy of Sciences Leopoldina, Germany (since 2011).

Abstract

The diversity of biological attachment structures is huge. By making a comparison of various attachment devices in biology we suggest that biological attachment systems can be subdivided into several groups according to the following principles: (i) fundamental physical mechanism, according to which the system operates, (ii) biological function of the attachment device, and (iii) duration of the contact. Eight fundamental attachment mechanisms have been previously recognized: (i) hooks, (ii) lock or snap, (iii) clamp, (iv) spacer or expansion anchor (v) suction, (vi) dry adhesion, (vii) wet adhesion (glue/cement, capillarity), and (viii) friction. Various combinations of these principles may also occur in real biological systems. From the biologists’ point of view, attachment devices may serve the following functions: (i) attachment of body parts to one another, (ii) attachment during copulation, (iii) phoresy or parasitism, (iv) dynamic attachment during locomotion, and (v) maintenance of position. According to the time scale of operation, different systems can be subdivided into three other groups: permanent adhesion, temporary adhesion and transitory adhesion. In this lecture, we discuss these classifications of biological attachment devices and draw some conclusions about the general relationships between the attachment mechanism and functional load of a biological attachment system. Finally, we show a biomimetic potential of studies of biological attachment devices.

Biography

Pietro Cicuta is a Reader in Biological Physics at the Cavendish Laboratory of Cambridge University. He obtained his PhD in 2003, and is presently active in research at the frontier between soft matter physics, optical methods and cell biology. He addresses question ranging from the regulation of gene expression in bacteria, to biological fluid flows, and mechanics and phase behaviour of lipid membranes. His lab uses and develops advanced imaging, photonic and microfluidic sample control, and quantitative modelling.

Abstract

Erythrocyte invasion by Plasmodium falciparum merozoites has been studied intensively, but our cellular understanding of invasion has been limited by the fact that invasion occurs very rapidly: it is generally complete in within one minute, and shortly thereafter the merozoites, at least in in-vitro culture, lose their invasive capacity. The rapid nature of the process, and hence the narrow time window in which measurements can be taken, have limited the tools available to observe invasion. Here we employ optical tweezers to study individual invasion events for the first time, showing that newly released P. falciparum merozoites, delivered via optical tweezers to a target erythrocyte, retain their ability to invade. Even spent merozoites that had lost the ability to invade still retain the ability to adhere to erythrocytes, and also can still induce transient local membrane deformations in the erythrocyte membrane. We use this technology to measure the strength of the adhesive force between merozoites and erythrocytes, and to probe the cellular mode of action of known invasion inhibitory treatments. These data have interesting implications for our current understanding of the cellular process of invasion, and demonstrate the power of optical tweezers technologies in unraveling blood stage biology of malaria.

Session 4: Viruses: contact and adhesion mechanisms

Dr Michaela Kendall, University of Southampton, UK
Process of nano-adhesion in the lung

Biography

Dr Kendall is an environmental scientist, with faculty-level experience in America, Asia and Europe. She specialised in the field of airborne particles, focussing on air pollution, nanoparticle toxicity in the lung, fuel cells (a clean energy technology) and policy development for atmospheric protection. In her early career, she studied air pollution impacts on materials and human health, specialising in the exposure measurement, nano-characterisation and health impact assessment of fine particulate matter (PM2.5) and nanoparticles (<100 nm). She currently develops fuel cells to reduce combustion emissions, primarily as a public health intervention with ancillary environmental benefits. Her career goal is to curtail combustion emissions to the atmosphere, to protect human and environment health. She was awarded the prestigious Rosenblith Prize by the HEI (www.healtheffects.org) in 2004, and is a Project Manager at Adelan with a Visiting Senior Lecturer Post at University of Southampton Medical School.

Abstract

During inhalation, airborne nanoparticles steadily diffuse to, and deposit on, the lung surface. The relatively sensitive, atmosphere exposed tissue of the lung has evolved to deal with nanoparticle exposure as a result. The primary defence is not cellular, but opsonisation by protein and lipid covering the lung surface which aggregates material to increase recognition and removal by macrophage clean-up cells. Proteomics of lung lining liquid shows how these protein components vary with individual, and even exposure history, thereby influencing the efficacy of this innate immune process that deals with both solid and biological nanoparticles e.g. combustion particles to viruses. Nano surface structure, plus adsorbed polymers, have long been known to influence the reception of material in the body, and new tools demonstrate nano-adhesive effects: For example, surface adsorbed polymer attachment to porous surfaces dictate the success of surgical implant materials, and the presence of plasma polymers in serum prevents platelet activation by agonist nanoparticles. In this session, we will compare viral/solid nanoparticle adhesion in biological systems, examine the role of adhesion in cell entry processes, and show how nanoparticle sequestration of polymers can affect virus infectivity.

Biography

David Bhella is a programme-leader in the Medical Research Council Centre for Virus Research at the University of Glasgow (CVR). His research focuses on the structural biology of viruses and virus-host interactions. He began his career working as a diagnostic virologist and electron microscopist in the Royal London hospital. Pursuing his interest in electron imaging of viruses he undertook his PhD at Birkbeck College London with Professor Helen Saibil FRS before moving to Glasgow to establish his own programme of virus structure research. His laboratory is currently investigating several virus systems including caliciviruses, hepatitis C virus, influenza virus, measles virus and respiratory syncytial virus.

David has a long standing interest in public engagement and working with schools audiences to enthuse students about careers in the sciences and in particular microbiology. Over the past decade he has built a thriving programme of outreach activities in the CVR in partnership with Glasgow Science Centre.

Abstract

As obligate intracellular parasites, viruses must traverse the host-cell plasma membrane to initiate infection. The first step in the viral entry pathway is engagement of a specific host macromolecule at the cell-surface. Several classes of molecule are exploited by diverse groups of viruses and many of these viral-receptors are involved in cell-adhesion. In particular immunoglobulin-like cell-adhesion molecules (IgSF CAMs) have been repeatedly identified as being critical for virus attachment and entry. One such example is Junctional Adhesion Molecule A, which is the receptor for Feline Calicivirus. Structure analysis of this virus-receptor complex provides valuable insights into the first stage of the infection process, identifying critical residues in both virus and receptor that are involved in attachment. Furthermore interaction with the receptor induces structural changes in the viral capsid in preparation for genome release. Comparison of these data with structural studies of other Ig-CAM binding viruses does not shed light on why these molecules are so widely used. Moreover their use is surprising given the often occluded position of CAMs on the cell surface, for example at tight-junctions. Nonetheless the reason for their widespread involvement in virus entry probably originates in their functional rather than structural characteristics.

Biography

Elspeth Garman is Professor of Molecular Biophysics and Director of the University of Oxford’s Doctoral Training Centre Systems Biology Programme. Her doctorate is in experimental nuclear physics, but after 7 years of further nuclear research, she changed fields to structural biology. As well as determining protein structures, some of which have been relevant to cell adhesion, her group works to improve methods for protein crystallography diffraction experiments. She has worked extensively to move macromolecular cryo-crystallographic techniques, and also the understanding of radiation damage effects during X-ray experiments, from anecdote to more firmly based methodology. Most recently, her group’s 3-D modelling of absorbed dose distributions in crystals during X-ray exposure have allowed new strategies for optimising diffraction data collections. She has also developed a high throughput microbeam Proton Induced X-ray Emission (microPIXE) technique for unambiguously identifying metals in proteins and determining their stoichiometric ratios accurately.

Abstract

Infection by the influenza virus depends firstly on cell adhesion via the sialic acid binding viral surface protein, haemagglutinin, and secondly on the successful escape of progeny viruses from the host cell to enable the disease to spread to other cells. To achieve the latter, influenza utilises another glycoprotein, the enzyme neuraminidase (NA), to cleave the sialic acid receptors from the surface of the original host cell. This talk will trace the development of anti-influenza drugs, from the initial suggestion by MacFarlane Burnet in 1948 that an effective “competitive poison” of the virus’ NA might be useful in controlling infection by the virus, through to the determination of the structure of NA by X-ray crystallography and the realisation of Burnet’s idea with the design of NA inhibitors. A focus will be the contribution of the late William Graeme Laver to this research.

Session 5: Molecular modelling by computer and mechanics

Biography

Costantino Creton graduated in Materials Science from the EPFL (Switzerland) in 1985. He then obtained his PhD in Materials Science and Engineering at Cornell University (USA). After a post-doc at the IBM Almaden Research Center (USA), he joined the ESPCI ParisTech first as a post-doctoral associate in 1993 and, since 1994 as a C.N.R.S. permanent researcher. He was promoted CNRS research director (equivalent to Professor) in 2001and since 2009, he is coordinating the research activities of the Soft Polymer Networks research group of the laboratory. He holds also since 2011 the position of scientific chairman of the Performance Polymers technology area of the Dutch Polymer Institute. He has published more than 130 articles in peer-reviewed journals, nine book chapters, more than 100 conference proceedings and has given more than 70 invited and plenary lectures at international conferences.

Abstract

Interfaces play a major role in how objects and materials interact. This is even more true when the objects have specific molecules on the surface that can interact chemically such as in cells. However even for simple materials, modelling such interfaces with molecular detail is still a major challenge. Most molecular simulations packages represent reality at a certain length scale and with some level of detail. The greater the detail, the smaller is the volume that can be simulated. The process of simplification of the ingredients of the model to reach larger representative volumes is called coarse-graining and is well developed in the bulk, ie. for materials and fluids that have a homogeneous composition over the volume of interest. Interfaces pose a particular challenge because the composition, by definition changes spatially and the length scale over which this composition changes is generally poorly known. Several simulations methods have been developed by different communities based on their specific interest: Cohesive zone modelling in the solid mechanics community to transfer stresses1, 2, A thermodynamic approach to simulate equilibrium composition for physicists3, 4. Polymer deformation at interfaces (cohesive vs adhesive transitions)5, 6. Coarse-graining simulation of adhesion between latex particles with soft potentials7.

Biography

Chin Yong is a member of Senior Research Scientist of the Scientific Computing Department at Daresbury Laboratory since 2000. He has extensive research experience in a wide-range of molecular modelling fields including polymers, particle bombardment, nano-surface contacts, mineral surface interactions and biological simulations, using a variety of techniques such as the molecular dynamics, Monte Carlo and ab-initio electronic calculations. Since 2010, he is also an active support scientist for the CCP5* community, in particular, in areas of potential model development. Chin Yong is also the developer of DL_FIELD, a powerful potential model development and editing software tool for DL_POLY (a molecular dynamics simulation software package) as a result of culmination of many years’ experiences in molecular modelling research.

*CCP5 is the Collaborative Computational Project for computer simulation of condensed phases. It provides and maintain software infrastructure for the UK research community and is funded predominantly by the EPSRC.

Abstract

We use molecular modelling techniques, namely the molecular dynamics (MD) simulations, to explore how polymer nanoparticles interact with the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid cell membranes. Two different polymers have been considered: polyethylene and polystyrene, both of which have wide industrial applications. We found that, despite the polar lipid headgroups can act as an effective barrier to prevent the nanoparticles from interacting with the membrane surface, irreversible adhesion can be initiated by insertion of dangling chain ends from the polymer into the hydrophobic interior of the membrane. In addition, alignment of chain segments from the polymers with that of hydrocarbon chains in the interior of the membrane facilitates the complete immersion of the nanoparticles into the cell membrane. These findings highlight the importance of the surface and the topological structures of the polymer particles that dictate the absorption behaviour on the membrane and, subsequently, induce the possible translocation into the cell.

Biography

Stephen Hart, PhD, is Professor of Molecular Genetics at the Institute of Child Health, University College London. He is a graduate of Liverpool University and received his PhD from the University of Cape Town in Microbial Genetics in 1992. His current research is in the development of nanoparticle technologies for genetic therapies of inherited diseases such as cystic fibrosis and paediatric cancers such as neuroblastoma. He has more than 100 publications in this field and is also an inventor on seven patent applications covering synthetic gene delivery technologies. He is the founder scientist of a spin-out company, Nanogenic Solutions Ltd. and is a current committee member for the American Society of Gene Therapy.

Abstract

Synthetic nanoparticles offer great promise in the development of nucleic acid-based therapies. Nanoparticles are self-assembling formulations, usually of cationic reagents, that package anionic nucleic acids and protect them from extracellular nucleases. In the transfection process, nanoparticles adhere to the target cell surface through receptors prior to endocytic uptake into the cell. Many different targeting ligands have been explored but we have developed short peptide ligands displayed on the surface of lipid-peptide nanocomplexes targeted to cell adhesion molecules such as integrins and ICAM-1. However, these, and most other self assembling nanoparticles, have a net positive charge on their surfaces, leading to non-specific binding, compromising cell specificity and in vivo biodistribution. Therefore we have developed anionic formulations that display a much higher degree of targeting specificity, while maintaining efficiency of transfection. Anionic nanocomplexes achieved widespread dispersal in the brain from a single dose with effective transfected gene expression or RNAi.

Session 6: Tracking nanoparticles to control adhesion

Biography

Professor Terry Tetley heads the Lung Cell Biology group within the division of the National Heart & Lung Institute, Faculty of Medicine, Imperial College London. Her research has focused on mechanisms of pulmonary inflammation, tissue injury and disease due to inhalation of airborne pollutants, including environmental particulate air pollution, asbestos, cigarette smoke, engineered nanoparticles and microbial material, focussing on their role in diseases such as chronic obstructive pulmonary disease, asthma, lung cancer and, more recently, cardiovascular disease. She initiated the Imperial College strategy on “Nanoparticles and Health” in 2006 and in her more recent work on ambient air pollution and engineered nanoparticles, she is addressing the role of oxidative stress, particle uptake and translocation, inflammatory mediator and signalling pathways in collaboration with a multidisciplinary group of scientists, from Imperial College, UK, Europe and the USA.

Abstract

When nanosized material is inhaled a significant proportion can access the respiratory, alveolar region. Although the immune cells, (eg macrophages) and epithelium are the first cellular targets at this interface, the first biological membrane is the alveolar surfactant, a surface tension reducing material, rich in phospholipids and containing unique surfactant-associated protiens, SP-A, SP-B, SP-C and SP-D. This brief presentation will describe how the behaviour and toxicity of nanomaterials can be affected by their interaction with lung surfactant, an important biological membrane at the gas-liquid interface of the lung.

Biography

André Nel is a Professor of Medicine and Chief/founder of the Division of NanoMedicine at UCLA. He is the Director of the UC Center for the Environmental Implications of Nanotechnology (UC CEIN), a major NSF and EPA-funded center for nanosafety implementation in the US. He also directs the NIH-funded UCLA Center for Nano Biology. UC CEIN is housed in the California NanoSystems Institute (CNSI) at UCLA, with affiliated faculty at several UC campuses. Dr. Nel obtained his medical (MD) and Doctorate of Medicine (PhD equivalent) degrees Stellenbosch in Cape Town, South Africa, and subsequently did Clinical Immunology training with board certification by the American Board of Internal Medicine as well as American Board of Allergy and Immunology. He directed the UCLA Asthma and Immunology Disease Center, with a major research focus on the study of air pollution and ambient ultrafine particles on asthma. Dr. Nel has been a member of the peer-selected Best Doctors of America since 1998, and has been the recipient of the John Salvaggio Memorial Award recognizing his outstanding service to the specialty and science of Allergy and Immunology, American Academy of Asthma Allergy and Immunology (AAAAI). He received the Harry Truman Lectureship award from Sandia National laboratories in 2012, while UC CEIN received the Governor’s Economic and Environmental Leadership Award (GEELA) in California in 2013. He has represented the NIH and the National Nanotechnology Initiative in cooperative research agreements with Japan, the Chinese Academy of Sciences and Russia. He is an Honorary Foreign Professor in the Chinese Academy of Sciences, and has served as a member of a distinguished NSF panel that produced a comprehensive US Government Science Report and vision for US nanotechnology research 2011-2020. He is Associate Editor of ACS Nano and has delivered several plenary and keynote lectures on asthma, nanotherapeutics and nanotoxicology at national and international conventions. Dr. Nel’s chief research interests are: (i) Nanomedicine and nanotherapeutics with particular emphasis on the development of nanoparticle treatment platforms that can be used for drug delivery, siRNA delivery and imaging (Dr. Nel co-directs the UCLA Nanomachine Center, housed in the CNSI); (ii) Nanobiology with particular emphasis on nanomaterial interfacial properties and quantitative structure-activity relationships to improve bio-processing, biosafety, and multifunctional nanocarrier design; (iii) Nanotechnology environmental health and safety, with particular emphasis on predictive toxicological modeling, high throughput safety screening, and safe implementation of nanotechnology in humans and the environment; (iv) The role of air pollutants in asthma, with particular emphasis on the role of oxidative stress in the generation of airway inflammation, allergic sensitization and asthma. His research is funded by personal (RO1) and center grants from the National Institute of Environmental Health Sciences, National Cancer Institutes, the EPA and the NSF. Dr. Nel and his collaborators have developed several pending or issued nanomaterial patents and he is an advisor to industry and several federal agencies.

Abstract

We have come to recognize that much of biology is executed at the nanoscale level, therefore providing a rational approach to using discovery about the structure and function of engineered nanomaterials (ENMs) at the nano/bio interface for interrogation of disease, diagnosis, treatment, and imaging at levels of sophistication not possible before. Moreover, the behavior of ENM’s at the nano/bio interface also constitutes the basis for hazard generation and is important for understanding safety assessment and safer design of nanomaterials. I will discuss how discovery at the molecular, cellular, organ and systemic nano/bio interfaces has assisted progress in development of nanocarriers. I will explain how the physicochemical properties of nanomaterials relate to nanoscale interactions at the membrane, intracellular organelles, tissues and organs, allowing adaptation of nanocarriers to negotiate cellular and systemic barriers as well as safer design. I will delineate how the use of high throughput screening to establish structure-activity relationships is used for design improvement of mesoporous silica nanoparticles to improve biodistribution and overcome the stroma of pancreatic cancer.

Biography

Dr Orest Blaschuk is a tenured Associate Professor at McGill University. He has worked in the field of cell adhesion for over two decades. In 1996, Dr Blaschuk co-founded Adherex Inc., a publicly traded McGill spin-off oncology company where he served as Chief Scientist (1996-2006) and consultant (2006-2009). Adherex developed anti-cancer drugs based on intellectual property generated in Dr Blaschuk's laboratory at McGill University. The Adherex drug ADH-1 reached Phase II clinical trials as an anti-cancer agent and was given orphan drug status by the FDA for the treatment of melanoma. Dr. Blaschuk thus has proven expertise in drug discovery and development from the laboratory to the clinic. Dr Blaschuk received his BSc, MSc and PhD degrees from the Universities of Winnipeg, Manitoba and Toronto, respectively. He has authored 73 scientific journal articles and book chapters. Dr Blaschuk is also named as an inventor on 49 US patents.

Abstract

This presentation will focus on the cell adhesion molecule, known as N-Cadherin. Five topics will be discussed:

The mechanism by which N-cadherin promotes cell adhesion,

Role of N-cadherin in tumor blood vessels,

Participation of N-cadherin in cancer progression,

Development of N-cadherin antagonists, and

N-cadherin antagonists as anti-cancer drugs.

Session 7: Chemical engineering of cells and applications

Biography

Professor Liam Grover’s research focuses on the interactions that occur between materials and biological systems. By enhancing our understanding of these interactions, he has been able to design implantable materials that are capable of initiating the tissue regeneration process. Prior to setting up his research group at the University of Birmingham, UK, he worked at McGill University in Montreal, where he specialised in the mechanisms known to influence the bone formation process. Professor Grover has published in excess of 100 papers, is named on five patent filings and has written four book chapters. He was one of the youngest researchers to be made a fellow of the institute of materials and was made one of the youngest professor’s in the history of the University of Birmingham at the age of 32.

Abstract

As the understanding of cell adhesion mechanisms improves, it is becoming possible to manipulate surface chemistry to initiate or prevent localised cell attachment. This control over adhesion is being applied in a diverse range of research areas. In regenerative medicine, for example, researchers are modifying material chemistry in order to prevent cell attachment and enable the expression of therapeutic factors or even to generate tissues ex-vivo by exploiting the natural ability of certain cell types to attach to or contract biologically derived matrices. Such systems are also being used to evaluate systematically how spatial patterning of localised cell adhesion can modify biological response. Avoiding cell adhesion is also important in many areas, and is being explored as a means to prevent fouling, either during industrial processing or plaque formation on the surface of enamel. Within this session, the speakers will explore how the control and systematic evaluation of cell adhesion will have a broad impact in areas including chemical engineering process design, to the development of personal care products, through to the restoration of biological function.

Biography

Otto-Wilhelm Merten has a degree in biotechnology (PhD) and today is the head of the group of Applied Vectorology and Innovation at Généthon. He has a large scientific experience gained during his stays at the Inst. Pasteur (Paris/F) as well as at the Sandoz Research Inst. (Vienna/A). Over the last 20 years, he has dealt with the development and optimization of serum-free and animal-free media for the cultivation of various cell lines (hybridomas, Vero, BHK 21, MDCK) and the production of different biologicals including monoclonal antibodies, recombinant proteins, various viruses. In addition, he was involved in the development of processes for the production of viruses for vaccine purposes (influenza, rabies, polio). During the last years he was involved in the development and scale-up of production and purification processes for viral vectors starting at the Inst. Pasteur in Paris and continuing as head of the department of Bioprocess Development at Généthon. Since 2010 he is in charge of the group of Applied Vectorology and Innovation (enabling technologies) in view of the general optimisation of vector production. Since expert in animal cell technology he was member of the executive committee of the European Society for Animal Cell Technology for 16 years and its chairman from 2001 to 2005. Otto-Wilhelm Merten is Adjunct Professor at the University of Life Sciences in Vienna and Visiting Professor at IBET/UNL in Lisbon.

Abstract

Although for large scale manufacturing cells, such rCHO or recombinant myeloma cells, growing in suspension are preferred due to their advantageous technological features, anchorage dependent cells are still of high interest mainly for the following two purposes: i) production of viral vaccines at bioreactor scale using microcarriers, and ii) generation of cells at small scale for cell therapy purposes (amplification of stem cells). In both cases, the culture system has to provide sufficient culture surfaces for cell growth, which is, in particular, critical at a large scale using bioreactors due to the inherent hydrodynamic issues related to the use of microcarriers. This can be alleviated by novel cell culture devices at least a medium scale. Passaging/subcultivating adherent cells is a general issue because the cells have to be detached from their support for inoculating subcultures. This is traditionally performed using proteases (“trypsinisation”) despite many drawbacks. The talk presents an update on novel technological and biological ways to perform cultures of anchorage dependent cells and to replace cell detachment by less damaging and gentler ways to preserve the cells’ geno- and phenotypic features for their subsequent use.

Biography

Birgitta Söder, professor em., in Odontological prophylaxis at the Karolinska Institutet, Department of Dental Medicine, Huddinge. Research activities involve epidemiological and clinical studies of the relationship between dental plaque- oral hygiene, gingival inflammation – periodontitis and systemic diseases, particularly the role of oral infections in cardiovascular diseases and cancer, including systemic makers relating cardiovascular and cancer diseases and periodontitis as well as the role of bacterial interactions. Other research areas of interest are the influence of anxiety and stress-related mental depression on periodontal health as well as tobacco related periodontal diseases. The overall goal is prevention of gingival inflammation and periodontitis. Dr Söder was 1998 awarded the IADR Oral Health Research Group Award and 2004 the IFDH, research award. Former President of the International Association for Dental Research: Oral health Research Group. She is currently research group leader for studies in collaboration with University of Helsinki, Finland as well as studies at University of Pisa.

Abstract

Dental plaque is a bacterial biofilm formed on dental surfaces. Dental plaque may also associate with systemic health and diseases due to hematogenic spread of oral microorganisms with subsequent up-regulation of cytokines and inflammatory mediators. For example, periodontitis is mediated by the inflammatory response to bacteria in the biofilm involving complex interactions with host defense.Our hypothesis was that oral-dental infections associate with a number of life threatening diseases such as cancer.

We investigated the association between oral-dental infections with systemic health in a cohort follow-up since 1985. The aim was to compare baseline oral examination data with specific diagnoses from Swedish national cancer-, hospital- and death register databases. Our results confirmed the hypothesis by showing significant association between dental plaque and death in cancer (p<0.001). Thus, chronic oral diseases indeed seem to have detrimental health consequences probably by maintaining an often neglected systemic inflammatory burden.

Session 8: Cancer cells and metastasis through low adhesion

Professor Kevin Kendall FRS, Chemical Engineering, University of Birmingham, UK
The next century prospect in cell adhesion

Biography

Professor Kevin Kendall received his PhD from Cambridge and has worked for 20 years in industrial research at ICI, and also 20 years in Universities at Monash, Akron, Keele and now Birmingham. He started his research career studying friction and adhesion and became interested in the energy balance method for calculating adhesion forces. He has applied this method to many different areas including adhesive joints, composites, slurries, nanoparticles, cells and viruses. He has also been involved in the fossil energy crisis and applies fuel cells to avoid carbon emissions, especially operating a fleet of hydrogen fuel cell vehicles with a filling station on the Birmingham University campus as shown in the picture. He is now back in industry, CEO of Adelan Ltd, an SME developing several EU projects. He has written more than 300 publications and patents and was elected FRS in 1993.

Abstract

The purpose of this final session is to consider the wonderful advances in cell adhesion science that have been described at this discussion meeting, then to analyse where future progress might occur. Harrison1 originally showed 100 years ago that animal cells required adhesion to a solid surface if they were to move, grow and reproduce. Following that invention of cultured cells, viruses could then be grown controllably within the cells so that the processes of virus attack and spread began to be understood. In a similar way, cultured cells have been exposed to nanoparticles in order to define how cell damage occurs. Further advances have been made in growing tissues and organs on special material substrates.How could this knowledge grow during the next century? First we review the questions about adhesion which have caused argument. Then follows a summary of the solutions to some of those controversies. Finally it is possible to speculate about potential advances and breakthroughs to come in future.Harrison,R.G., The reaction of embryonic cells to solid structures, J Expt Zool 17(1914)521-44.

Biography

Rik Bryan qualified in Medicine at the University of Birmingham and subsequently entered surgical training. After completing a PhD in bladder cancer biology he became a Specialist Registrar in Urology. After 4-years as a Specialist Registrar, Rik left clinical urology to assist with the set-up of the Bladder Cancer Prognosis Programme at the University of Birmingham, and was then subsequently appointed as a Senior Research Fellow in the School of Cancer Sciences. Rik is now the Chief Investigator of the Bladder Cancer Prognosis Programme which incorporates the SELENIB clinical trial, and is also a member of the Trial Management Group for the POUT trial with responsibility for biospecimen collection and translational research. Rik sits on the Council of The Royal Society of Medicine Section of Urology, and has been elected as Secretary for the section for the 2015-16 session, and is also a regular Reviewer for European Urology.

Abstract

Cadherins are the main mediators of cell-cell adhesion in epithelial tissues. E-cadherin is a known tumour suppressor and plays a central role in suppressing the invasive phenotype of cancer cells. However, the abnormal expression of other cadherins (“cadherin switching”) has been shown to promote a more invasive and malignant phenotype of cancer, with P-cadherin possibly acting as the principal mediator of invasion and metastasis in bladder cancer. Cadherins are also implicated in numerous signalling events related to embryonic development, tissue morphogenesis, and homeostasis. It is these wide-ranging effects and the serious implications of cadherin switching that make the cadherin cell adhesion molecules and their related pathways strong candidate targets for the inhibition of cancer progression, including bladder cancer. This lecture will focus on cadherin switching in the context of bladder cancer and will discuss other related molecules and phenomena, including EpCAM and the development of the cancer stem cell phenotype.

Memberships and Fellowships: Member, American Academy of Arts and Sciences, National Academy of Sciences, National Academy of Engineering, American Philosophical Society; Fellow of the American Association for the Advancement of Science, Institute of Physics, American Physical Society, New York Academy of Sciences, World Technology Network, and American Chemical Society; Foreign Fellow of the Indian National Academy of Science; Honorary Member of the Materials Research Society of India; Honorary Fellow of the Chemical Research Society of India, Royal Netherlands Academy of Arts and Sciences, Royal Society of Chemistry (UK); Foreign Associate of the French Academy of Sciences; Honorary Professor, Academy of Scientific and Innovative Research (AcSIR), India.